The addition of nimotuzumab during concurrent chemoradiotherapy improved survival outcomes in locally advanced nasopharyngeal carcinoma patients with optimal response to induction chemotherapy.

OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.

Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prognostic significance of the skeletal muscle index and systemic inflammatory index in patients with lymph node-positive breast cancer after radical mastectomy.

BACKGROUND: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population. METHODS: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model. RESULTS: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36). CONCLUSIONS: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study.

Local treatment improves survival in patients with stage IVB cervical cancer.

OBJECTIVE: To evaluate the value of local treatment in stage IVB cervical cancer (CC). METHODS: Patients diagnosed with stage IVB CC between 2010 and 2015 were included using the data from the Surveillance, Epidemiology, and End Results program. Propensity score matching (PSM) was used to balance the clinicopathological variables of patients. Multivariate Cox regression analyses were performed to analyze the risk factors associated with cause-specific survival (CSS). RESULTS: We identified 960 patients in this study, all patients had received chemotherapy. Of these patients, 818 patients were treated with local treatment (85.2%), including 724 (88.5%) and 94 (11.5%) patients receiving radiotherapy (RT) alone and surgery ± RT, respectively. Local treatment was the independent prognostic factor associated with better CSS. Before PSM, patients who received RT (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.517-0.775, P < 0.001) or surgery (HR 0.391, 95% CI 0.277-0.552, P < 0.001) were independently associated with a better CSS compared to those with no local treatment. The 3-years CSS rate was 14.4%, 32.4%, and 54.8% in no local treatment, RT alone, and surgery groups, respectively (P < 0.001). Similar results were found after PSM. Patients receiving RT (HR 0.643, 95% CI 0.436-0.947, P = 0.025) and surgery (HR 0.146, 95% CI 0.052-0.410, P < 0.001) had better CSS compared to patients with no local treatment after PSM. While similar CSS was shown between RT alone cohort and the surgery cohort (HR 0.756, 95% CI 0.454-1.260, P = 0.284). CONCLUSIONS: The addition of local surgery or RT to chemotherapy appears to confer improved survival outcomes in patients with stage IVB CC.

circ-PTK2 (hsa_circ_0008305) regulates the pathogenic processes of ovarian cancer via miR-639 and FOXC1 regulatory cascade.

BACKGROUND: Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. METHODS: CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial-mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. RESULTS: CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. CONCLUSIONS: circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.

Adjuvant chemotherapy and survival outcome in node-negative breast cancer with a 21-gene recurrence score of 26-30.

Aim: To investigate the benefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scores of 26-30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patients received adjuvant chemotherapy. Patients with higher tumor grade, larger tumors and younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patients without chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated or undifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26-30, especially for patients with high-grade tumors.

Lay abstract In current clinical practice, the 21-gene recurrence score has been developed for chemotherapy decision-making based on prognostic risk stratification, especially for patients with tumor size ≤5 cm, node-negative, hormone receptor-positive and HER2-negative breast cancer. However, the chemotherapy benefit in breast cancer patients with a 21-gene recurrence score (RS) of 26­30 is unclear. This study aimed to investigate the survival benefit of additional chemotherapy for early-stage breast cancer patients with RS 26­30 using the Surveillance, Epidemiology, and End Results data. Our study suggests that the RS 26­30 group is regarded as a uniform entity by clinicians. Adjuvant chemotherapy improves the outcome for early-stage breast cancer patients with RS 26­30, especially for patients with high-grade tumors.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer.

BACKGROUND: The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. METHODS: Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. RESULTS: Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642-0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3-4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1-2N1 disease (P = 0.191). CONCLUSIONS: Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3-4N1 and T1-4N2-3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1-2N1 TNBC.

Histological Tumor Type is Associated with One-Year Cause-Specific Survival in Women with Stage III-IV Epithelial Ovarian Cancer: A Surveillance, Epidemiology, and End Results (SEER) Database Population Study, 2004-2014.

BACKGROUND The prognosis of epithelial ovarian cancer (EOC) remains poor. Cause-specific survival (CSS) is an overall survival measure of cancer survival that excludes other causes of death. This retrospective population study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors associated with one-year CSS in women with stage III-IV EOC between 2004-2014. MATERIAL AND METHODS Data from the SEER program included a cohort of patients with stage III-IV EOC between 2004-2014. Binomial logistic regression analysis, Kaplan-Meier survival curves, and multivariate Cox proportional hazards models were used for analysis of patient outcome, including the one-year CSS. RESULTS There were 14,798 patients with stage III-IV EOC identified from SEER between 2004-2014, including 13,134 (88.8%), 892 (6.0%), 448 (3.0%), and 324 (2.2%) patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively. The overall one-year CSS was 91.2%. One-year CSS was 92.5%, 92.2%, 74.0%, and 62.5% in patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively (P<0.001). Histological tumor type was an independent prognostic factor of one-year CSS. Patients with mucinous EOC (HR, 8.807; 95% CI, 6.563-9.965; P<0.001) and clear cell EOC (HR, 4.581; 95% CI, 3.774-5.560; P<0.001) had a significantly lower one-year CSS compared with patients with endometrioid and serous EOC who had comparable one-year CSS (HR, 1.247; 95% CI, 0.978-1.590; P=0.075). CONCLUSIONS A retrospective population study of the SEER database between 2004-2014 identified that histological tumor type was associated with one-year CSS in women with stage III-IV EOC.

The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.

Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.

Inflammatory breast cancer outcomes by breast cancer subtype: a population-based study.

AIM: To assess the outcomes of breast cancer subtype in inflammatory breast cancer (IBC). METHODS: We retrospectively assessed IBC patients from the SEER program. RESULTS: We identified 626 patients, including 230 (36.7%),100 (17.6%), 113 (18.1%), and 173 (27.6%) patients with HoR+/HER2-, HoR+/HER2+, HoR-/HER2+, and HoR-/HER2- subtype disease, respectively. Multivariate analysis demonstrated that, using HoR+/HER2- subtype as reference, patients with HoR+/HER2+ subtype had better breast cancer-specific survival (BCSS) and overall survival (OS), and patients with HoR-/HER2- subtype had worse BCSS and OS, while BCSS and OS were comparable for HoR-/HER2+ subtype. Similar trends were observed in patients who received surgery, radiotherapy, chemotherapy or trimodality therapy. CONCLUSION: Breast cancer subtype is clinically useful for predicting survival outcome in IBC. The HoR+/HER2- subtype shows poorer survival outcome than HoR+/HER2+ subtype.

The 1-year mortality after radiotherapy for nasopharyngeal carcinoma: a population-based analysis.

Aim: To assess the incidence and predictors of nasopharyngeal carcinoma (NPC)-specific mortality in the first year among NPC patients. Methods: We identified 2714 patients in the SEER program. Results: Of the patients, 151 (5.6%) patients who died as NPC-related disease within 1 year of diagnosis. Specifically, 67.5% of the NPC-related deaths were attributed to keratinizing tumors, while 67.6% were attributed to advanced T stage. Older age, keratinizing squamous tumors and stage T3-4 disease were independent predictors of 1-year NPC-related death. Conclusion: The 1-year mortality rate is low among NPC patients after radiotherapy. Older age, keratinizing tumor and advanced T stage are predictors of high-mortality risk within 1 year in NPC patients.

Lung Large Cell Neuroendocrine Carcinoma: An Analysis of Patients from the Surveillance, Epidemiology, and End-Results (SEER) Database.

BACKGROUND The aim of this study was to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes in lung large cell neuroendocrine carcinoma (LCNEC). MATERIAL AND METHODS Patients diagnosed with lung LCNEC between 2000 and 2013 were identified using the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier methods and univariate and multivariate analyses were used for statistical analysis. RESULTS A total of 2097 patients were identified. The total age-adjusted incidence rate of lung LCNEC was 0.3/100 000, with a rise in incidence over the study period. The 5-year lung cancer-specific survival (LCSS) and overall survival (OS) were 20.7% and 16.7%, respectively. Multivariate analysis indicated that age ³65 years, male sex, advanced tumor stage, advanced nodal stage, not undergoing surgery. and not undergoing chemotherapy were independent adverse indicators for survival outcomes. After stratification by tumor stage, undergoing surgery was associated with more favorable LCSS and OS compared with those without surgery, regardless of tumor stage. CONCLUSIONS LCNEC is a rare lung cancer subtype with a dismal prognosis. Primary surgical treatment has significant survival benefits, even for stage IV patients. The optimal treatment strategies for lung LCNEC require further investigation.

The Role of Axillary Lymph Node Dissection in Tubular Carcinoma of the Breast: A Population Database Study.

BACKGROUND The aim of this study was to investigate the role of axillary lymph node dissection on the outcome of patients with tubular carcinoma of the breast. MATERIAL AND METHODS Patients diagnosed with tubular carcinoma of the breast between 2000-2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analysis of the data was undertaken, including analysis of breast cancer-specific survival (BCSS). RESULTS Of the 5,645 patients identified on the SEER database with tubular carcinoma of the breast, 5,032 (89.4%) patients had undergone axillary lymph node dissection, with significantly increased rates after 2002 compared with rates between 2000-2001 (p <0.001), which stabilized between 2002-2013 (p=0.330). Axillary lymph node metastases were present in 6.1% of all patients and in 5.3% of patients with a tumor size ≤2 cm. Lymph node-positive disease was associated with patient age ≤65 years, intermediate-grade or high-grade tumors, and tumor size >2.0 cm. Axillary lymph node dissection was an independent prognostic indicator. The 10-year BCSS was 97.3% and 96.6% in patients with and without axillary lymph node dissection, respectively (p=0.002). The number of removed lymph nodes was not related to breast cancer-specific survival. CONCLUSIONS In patients with tubular carcinoma of the breast, lymph node status was not associated with significant breast cancer-specific survival. However, axillary lymph node dissection may still be considered for patients with for tubular carcinoma of the breast even in patients with a small tumor size.

Survival benefits with the addition of adjuvant hysterectomy to radiochemotherapy for treatment of stage I-II adenocarcinoma of the uterine cervix.

BACKGROUND AND OBJECTIVES: To determine the survival benefits of additional adjuvant hysterectomy in the International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical adenocarcinoma patients treated with radiochemotherapy. METHODS: Patients with FIGO stage I-II cervical adenocarcinoma were selected from the Surveillance, Epidemiology, and End Results 18 Regs research database. Propensity score matching (PSM) was used to balance patient baseline characteristics. Patient characteristics and outcomes were compared between the two groups. RESULTS: A total of 530 patients were included, 389 (73.4%) underwent definitive radiochemotherapy and 141 (26.6%) underwent an additional adjuvant hysterectomy. The multivariate Cox analysis surgery was shown to be an independent predictor of survival. Before PSM, the hazard ratios for cause-specific survival and overall survival in the surgery group were 0.632 (P = 0.036) and 0.674 (P = 0.041), respectively. After PSM, the respective hazard ratios were 0.392 (P < 0.001) and 0.465 (P = 0.001). The surgery group had significantly better 5-year cause-specific survival (80.5% vs 59.1%; P = 0.001) and overall survival than the nonsurgery group (76.3% vs 56.0%; P = 0.002). CONCLUSIONS: Additional adjuvant hysterectomy after radiochemotherapy may improve survival outcomes in patients with FIGO stage I-II cervical adenocarcinoma.

Widowed status increases the risk of death in vulvar cancer.

AIM: To evaluate the effect of marital status on survival of patients with vulvar cancer. MATERIALS & METHODS: A total of 4001 patients with vulvar cancer were included from the SEER database. Statistical analyses were performed using χ2 test, Kaplan-Meier method, Cox regression proportional hazards and a 1:1 propensity score-matching. RESULTS: The 8-year vulvar cancer-related survival in married, divorced, single and widowed patients were 78.6, 82.2, 78.9 and 61.6%, respectively (p < 0.001). In multivariate analysis, widows patients had significantly worse vulvar cancer survival than the nonwidowed counterparts in unmatched and matched populations. CONCLUSION: Being widowed is associated with greater risk of vulvar cancer mortality than the nonwidowed counterparts.

Lymph node ratio has prognostic value related to the number of positive lymph nodes in patients with vulvar cancer.

AIM: We investigated the value of the number of positive lymph nodes (PLNs) and lymph node ratio (LNR) on survival of vulvar cancer patients. METHODS: A total of 2332 patients with vulvar squamous cell carcinoma were included from the SEER program. RESULTS: In multivariate analysis, the number of PLNs and LNR were independent prognostic indictors of survival outcomes, a higher number of PLNs and a higher LNR had poorer survival outcomes. An LNR >0.2 was associated with poor survival outcomes according to the number of PLNs. CONCLUSION: The LNR has prognostic value related to the number of PLNs and may allow a more accurate determination of the lymph node status of vulvar cancer patients.

Tubular carcinomas of the breast: an epidemiologic study.

AIM: We explored the clinicopathologic characteristics, prognostic factors and outcomes in tubular carcinoma (TC) of the breast. METHODS: We retrospectively assessed 8091 TC patients using the SEER database from 2000 to 2013. RESULTS: Most patients were non-Hispanic white, well-differentiated disease, tumor size ≤2 cm, node-negative, nonmetastatic, hormone receptor-positive and HER2-negative status. The 10-year breast cancer-specific survival and overall survival were 98.1 and 82.0%, respectively. Multivariate analysis indicated that age, ethnicity, surgery procedures, radiotherapy and chemotherapy were independent predictors affecting survival outcomes. There was comparable breast cancer-specific survival between surgery and nonsurgery groups. CONCLUSION: The patients with TC has excellent survival outcomes, which may in part be due to the favorable tumor characteristics.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Number of negative lymph nodes is associated with disease-free survival in patients with breast cancer.

BACKGROUND: The aim of this study was to evaluate the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients after mastectomy. METHODS: 2,455 breast cancer patients who received a mastectomy between January 1998 and December 2007 were retrospectively reviewed. The prognostic impact of the number of NLNs with respect to disease-free survival (DFS) was analyzed. RESULTS: The median follow-up time was 62.0 months, and the 5-year and 10-year DFS was 87.1% and 74.3%, respectively. The DFS of patients with >10 NLNs was significantly higher than that of patents with ≤10 NLNs, and the 5-year DFS rates were 87.5% and 69.5%, respectively (P < 0.001). Univariate Cox analysis showed that the NLN count (continuous variable) was a prognostic factor of DFS (hazard ratio [HR] = 0.913, 95% confidence interval [CI]: 0.896-0.930, P < 0.001). In multivariate Cox analysis, patients with a higher number of NLNs had a better DFS (HR = 0.977, 95% CI: 0.958-0.997, P = 0.022). Subgroup analysis showed that the NLN count had a prognostic value in patients at different pT stages and pN positive patients (log-rank P < 0.001). However, it had no prognostic value in pN0 patients (log-rank P = 0.684). CONCLUSIONS: The number of NLNs is an independent prognostic factor of DFS in breast cancer patients after mastectomy, and patients with a higher number of NLNs have a better DFS.